Field
The present invention relates to devices, systems and methods for quantifying, analyzing and/or identifying chemical species. More specifically, the present invention relates to devices, systems and methods for the conversion of certain molecular components of aerosols and liquid phase samples to gaseous molecular ions through a surface impact phenomenon which disintegrates aerosol particles or liquid jets into smaller particles including gas-phase molecular ions.
Description of the Related Art
Mass spectrometry is generally used for the investigation of the molecular composition of samples of arbitrary nature. In traditional mass spectrometric analysis procedures, the molecular constituents of samples are transferred to their gaseous phase and the individual molecules are electrically charged to yield gas-phase ions which can then be subjected to mass analysis, such as separation and selective detection of the ions based on their different mass-to-charge ratios.
Since certain molecular constituents are non-volatile, the evaporation of these compounds is not feasible prior to electrical charging. Traditionally, chemical derivatization was used to enhance the volatility of such species by eliminating polar functional groups. However, chemical derivatization also fails in case of larger molecules, representatively including oligosaccharides, peptides, proteins, and nucleic acids. In order to ionize and mass spectrometrically investigate these species of biological relevance, additional ionization strategies have been developed, including desorption and spray ionization.
In desorption ionization (excepting field desorption), condensed phase samples are bombarded with a beam of high energy particles, known as an analytical beam, to convert the condensed phase molecular constituents of samples into gaseous ions in a single step. The low sensitivity of this technique combined with its incompatibility with chromatographic separation hinders its general applicability to the quantitative determination of biomolecules in biological matrices. The poor sensitivity from which desorption ionization methods suffer is generally associated with the fact that most of the material is desorbed in the form of large molecular clusters with low or no electric charging. Recently, a number of methodological approaches have been described for converting these clusters into gaseous ions using a process termed secondary ionization or post-ionization. These methods employ a second ion source producing a high current of charged particles which efficiently ionizes the aerosol formed on the desorption ionization process.
Spray ionization methods were developed as an alternative to desorption ionization techniques and were intended to address the same problems addressed by desorption ionization—the ionization of non-volatile constituents of arbitrary samples. In spray ionization, liquid phase samples are sprayed using electrostatic and/or pneumatic forces. The resulting electrically charged droplets produced by the spraying are gradually converted to individual gas-phase ions upon the complete evaporation of the solvent. Spray ionization methods, particularly electrospray ionization, show superior sensitivity when compared to the desorption ionization methods mentioned above as well as excellent interfacing capabilities with chromatographic techniques (something for which desorption ionization was unsuccessful).
While theoretically spray ionization methods are able to provide nearly 100% ionization efficiency, such a high value is generally not reached because of practical implementation issues. Nanoelectrospray, or nanospray, methods give very high ionization efficiency but are limited to extremely low flow rates; such methods can only give high ionization efficiency for flow rates in the low nanoliter per minute range. Since practical liquid chromatographic separations involve higher liquid flow rates (e.g., including high microliters per minute to low milliliters per minute), nanospray is not the usual method of choice for liquid chromatographic-mass spectrometric systems. Pneumatically assisted electrospray sources are theoretically capable of spraying liquid flow in such ranges; however their ionization efficiency falls precipitously to the 1-5% range. Similarly to desorption ionization methods, spray ionization sources also produce considerable amounts of charged and neutral clusters which decreases ionization efficiency and can tend to contaminate mass spectrometric atmospheric interfaces.
The atmospheric interface of a mass spectrometer is designed to introduce ions formed by spray or atmospheric pressure desorption ionization to the vacuum regime of the mass spectrometer. The basic function of the atmospheric interface is to maximize the concentration of ions entering the mass spectrometer while reducing the amount or concentration of neutral molecules entering the mass spectrometer (e.g., air, solvent vapors, nebulae seen gases, etc.). The currently used approach in commercial instruments is to introduce the atmospheric gas into the mass spectrometer vacuum chamber and sample the core of the free supersonic vacuum jet using a skimmer electrode. Such an approach is based on the assumption that the ions of interest have a lower radial velocity component and will therefore be concentrated in the central core of the gas jet. The skimmer electrode is generally followed by radio-frequency alternating potential driven multi-pole ion guides which transmit the ionic species to the mass analyzer while the neutrals are statistically scattered and pumped out by the vacuum system. Such a combination of skimmer electrode and radio-frequency alternating potential driven multi-pole ion guides can allow up to 30% ion transmission efficiency; however, it does not solve or manage the problem of contamination by larger molecular clusters.
Further developments to mass spectrometers included the addition of a circular electrode around the rim of the skimmer electrode used to deflect more charged species into the opening of the skimmer electrode. The ring electrode, or “tube lens” as it is sometimes called, also allows the shift of the skimmer electrode sideways from the co-axial position relative to the first conductance limit. The offset can be partially compensated by applying electrostatic potential to the tube lens. Positioning the skimmer electrode in such a manner stops neutrals of arbitrary size (including clusters) from entering into the high vacuum regime of the mass spectrometer.
Another atmospheric interface configuration includes the introduction of ion-carrying atmosphere directly into a ring electrode ion guide. Bipolar radiofrequency alternating current is applied to a stack of ring electrodes thereby creating a longitudinal pseudo-potential valley for charged species, while neutrals are able to leave the lens stack by passing in between the individual electrodes. An electrostatic potential ramp (or a traveling wave) can be used to actively accelerate ions towards the mass spectrometric analyzer. Such devices, generally known as “ion funnels” can give close to 100% ion transmission efficiency in ion current ranges three to four orders of magnitude wide. Ion funnels have been modified in various ways to minimize the influx of neutrals and molecular clusters into the ion optics and mass analyzer. The simplest such solution includes the mounting of a jet-disruptor in the central axis of the funnel to block the trajectory of neutrals and molecular clusters flying through the ion funnel. Alternate solutions include: an asymmetric funnel geometry in which the exit orifice of the funnel is in an off-axis position relative to the atmospheric inlet; and twin-funnels in which the ion-carrying atmospheric gas is introduced into one funnel and the ions extracted sideways into a contralateral funnel, which is later connected to the ion optics of the instrument, using an electrostatic field(s).
However, there is a need for improved systems and methods for the conversion of liquid samples into gaseous ions.